4-Pyrones, 2,3-dihydro-, synthesis

Furo[2,3-amino-synthesis, 4, 986 Furo[3,4-d]pyrimidinedione synthesis, 4, 987 Furopyrimidines, 4, 986 Furo[2,3-d]pyrimidines synthesis, 4, 986 Furo[3,2-d]pyrimidines synthesis, 4, 987 Furo[3,2- 6]pyrone synthesis, 4, 994 Furo[3,2-c]pyrone synthesis, 4, 993 Furo[3,2-6]pyrrole, hexahydro-biological activity, 6, 1024 1 H-Furo[3,4-6]pyrrole-2,3-dione, 4,6a-diphenyl-6-(phenylimino)-6,6a-dihydro-synthesis, 6, 1004 Furopyrroles... 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

Two approaches, based on furan, have found wide application in carbohydrate synthesis. Cycloaddition reactions of furan with 2-substituted acrylonitrile or acrolein lead to oxabicycloheptanes which, in tnm, can be transformed to monosaccharides. On the other hand, furfuryl alcohols can be converted—either by the Clauson-Kaas reaction or by mild oxidation—into 5,6-dihydro-4-pyrones, suitable for easy functionalization to sugars. 

The HDA reaction allows for rapid access to chiral six-membered heterocyclic structures that serve as valuable intermediates in organic synthesis. The first highly enantioselective HDA reaction promoted by a chiral hydrogen bond donor was reported from the Rawal laboratory. While investigating the cycloaddition reactions of amino-siloxy diene 115, it was observed that this diene was exceptionally reactive to heterodienophiles, and underwent HDA reactions with various aldehydes at room temperature, even in the absence of any added catalyst (Scheme 6.14). Subsequent treatment of the intermediate cycloadducts (116) with acetyl chloride afforded the corresponding dihydro-4-pyrones (117) in good overall yields [101]. Further studies of this reaction revealed a pronounced solvent effect,... 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

Sato, M., Sunami, S., Kogawa, T., Kaneko, C. An efficient synthesis of cis-hydroindan-5-ones by novel modified de Mayo reaction using 2,3-dihydro -pyrones as the enone chromophore. Chem. Lett. 1994, 2191-2194. 

Carlson and Olger have reacted the dilithium salt of propargylic acid with oxiranes and shown that the resulting 8-hydroxycarboxylic acids could be cyclized wiA solvation to 5,6-dihydro-2-pyrones (Scheme 14). The method was subsequently used in a neat synthesis of pestalotin (R = Bu"CHMe). 

Dihydro-y-pyrones and dihydro-3-furanones.1 A new synthesis, of dihydro-y-pyrones (5) and dihydro-3-furanones (8) involves conversion of (1) into 2-lithio-2-(2 >2 -dimethoxyethyl)-l,3-dithianc (2) by treatment with n-butyllithium in THF at -30°. Treatment of (2) with an epoxide gives (3). On treatment with p-toluenesulfonic... 

Pyrone itself can be prepared via Prins alkylation of but-3-enoic acid with subsequent lactonisation, giving 5,6-dihydro-2-pyrone, which, via allylic bromination and then dehydrobromination, is converted into 2-pyrone. Alternative manipulation of the dihydropyrone affords a convenient synthesis of a separable mixture of the important 3- and 5-bromo-2-pyrones (see 11.2.2.4). 

Dihydro-4-pyrones are useful intermediates, particularly for the synthesis of carbohydrates. Addition of an activated diene with the carbonyl group of chiral... 

In a new synthesis of azepines, it has been shown that 2/f-pyrones react with 2-aminocinnamates to form 2,3-dihydro-l/f-azepine derivatives <89HCA457> in a reaction which has potential for the synthesis of a number of polycyclic azepines (Scheme 26). 

In the same year Tsuda et al. (27) reported the isolation of cytotoxic sesterterpenes from the Okinawan marine sponge Luffariella sp. among which was a compound with a 5,6-dihydro-a-pyrone moiety, luffariolide E. This compound showed cytotoxicity against murine leukaemia LI210 cells (IC50 1.1-7.8 pg/ml) in vitro. The original structure, which rested on chemical and spectroscopic evidence, has been corrected by synthesis to (24) (28). 

Related to this methodology is another one recently developed by Kirsch et al. [61], in which (Z)-aUylic alcohols are first converted into their trichloroacetimidates, and the latter are then subjected to a catalytic Sj 2 substitution of the trichloroace-timidate by a carboxylate group under the influence of complex 132, available in both enantiomeric forms (Scheme 2.26). If a p,y-unsaturated acid is used, an allyl P,y-unsaturated ester is obtained, which, after RCM and base-catalyzed migration of the double bond, affords a 5,6-dihydro-a-pyrone. The authors demonstrated the practical applicabihty of this methodology with the synthesis of (-)-rugulactone and other natural products. 

Contents M.T. Davies-Coleman and D. E. A. Rivett Naturally Occurring 6-substituted 5,6-dihydro-a-pyrones -K. Krohn Building Blocks for the Total Synthesis of Anthracyclinones - M. Lounasmaa and J. Galambos Indole Alkaloid Production in Catharanthus Roseus Cell Suspension Cultures -C. E. James, L. Hough, and R. Khan Sucrose and Its Derivatives. 

In addition to the considerable variety of methods for the synthesis of non-fluorinated y-pyrones [2], Tyvorskii and co-workers have described three new procedures, which produced 2-(perfluoroalkyl)-4-pyrones. One of them is a convenient two-step synthesis of 5-substituted 2-(perfluoroalkyl)-4 f-pyran-4-ones 2 by dehydration of 2,3-dihydro-3-hydroxy-6-(perfluoroalkyl)-4 f-pyran-4-ones 1 prepared... 

Tyvorskii VI, Stanishevskb LS, Tishchenko IG (1976) Synthesis of 3-hydroxy-6-perfluoroalkyl-2,3-dihydro-4-pyrones. Khim Geterotsiki Soedin 1575 Chem Abstr (1977) 86 139750... 

Sosnovskikh VY, Mel nikov MY, Pogozhikh SA (1999) Reactions of 3,3-dialkyl-2,3-dihydro-6-trifluoromethyl-4-pyrones with hydroxylamine. Synthesis tmd structures of 5-( 1, l-ditdkvl-2-hydroxyethyl)-5-hydroxy-3-trilluoromethyl-AMsoxazoUnes. Russ Chem BuU 48 1323-1328... 

Shao L, Kawano H, Saburi M, Uchida Y. Asymmetric hydrogenation of 3,5-dioxoesters catalyzed by Ru-binap complex a short step asymmetric synthesis of 6-substi-tuted 5,6-dihydro-2-pyrones. Tetrahedron 1993 49 (14) 1997-2010. 

---